(2S, 3S, 5S)-2,5-Diamino-1,6-diphenyl-3-hydroxyhexane derivatives are known to be useful as intermediates for retrovirus protease inhibitors (JP-A-4-308574, International Publication No. W094/14436, etc.). Methods for synthesizing the derivatives are known, including a method in which (2S, 3R, 4S, 5S)-3-acetoxy-2,5-bis-(N-benzyloxycarbonylamino)-4-bromo-1,6-diphenylhexan e derived from N-benzyloxycarbonyl-L-phenylalaninal is reacted with tri-n-butyltin hydride and 2,2'-azobis(2-methylpropionitrile) to give (2S, 3S, 5S)-3-acetoxy-2,5-bis(N-benzyloxycarbonylamino)-1,6-diphenylhexane (JP-A-4-308574 and International Publication No. W094/14436, referred to as synthesizing method A), a method in which (2S, 4S, 5S)-5-tert-butoxycarbonylamino-4-tert-butyidimethylsilyloxy-6-phenyl-2-(ph enylmethyl)hexanoic acid is reacted, in the presence of triethylamine, with diphenyl phosphorazidate [(PhO).sub.2 P(O)N.sub.3 ] and further with benzyl alcohol to give (2S, 3S, 5S)-2-tert-butoxycarbonylamino-3-tert-butyidimethylsilyloxy-5-benzyloxycar bonylamino-1,6-diphenylhexane (J. Org. Chem., 1993, 58, 1025, referred to as synthesizing method B), a method in which (2S, 4S, 5S)-5-tert-butoxycarbonylamino-4-tert-butyldimethylsilyloxy-6-phenyl-2-(ph enylmethyl)hexanoic acid is reacted, in the presence of triethylamine, with diphenyl phosphorazidate [(PhO).sub.2 P(O)N.sub.3 ] and further with 3-pyridylcarbinol to give (2S, 3S, 5S)-2-tert-butoxycarbonylamino-3-tert-butyldimethylsilyloxy-5-(3-pyridylme thoxycarbonylamino)-1,6-diphenylhexane (J. Org. Chem., 1993, 58, 1025 and Tetrahedron, 1993, 49, 8739, referred to as synthesizing method C), a method in which (5S)-2-amino-5-(N,N-dibenzylamino)-4-oxo-1,6-diphenylhexa-2-ene is first reacted with sodium borohydride which has been treated with methanesulfonic acid and further reacted with sodium borohydride which has been treated with trifluoroacetic acid to give (2S, 3S, 5S)-5-amino-2-N,N-dibenzylamino-3-hydroxy-1,6-diphenylhexane (International Publication No. WO94/14436 and J. Org. Chem., 1994, 59, 4040, referred to as synthesizing method D), and a method in which (5S)-2-(tert-butoxycarbonylamino)-5-(N,N-dibenzylamino)-1,6-diphenyl-4-oxo -2-hexene is first reacted with diborane tetrahydrofuran complex and further reacted with lithium aluminum hydride or potassium borohydride to give (2S, 3S, 5S)-2-N,N-dibenzylamino-5-(tert-butoxycarbonylamino)-3-hydroxy-1,6-dipheny lhexane (International Publication No. W094/14436, referred to as synthesizing method E).
However, synthesizing method A (JP-A-4-308574) has drawbacks that it uses heavy metal reagents such as vanadium, zinc, and tin in the synthesis route including the synthesis of starting materials and that the reaction must be carried out at an extremely low temperature.
Synthesizing method B (J. Org. Chem., 1993, 58, 1025) and synthesizing method C (J. Org. Chem., 1993, 58, 1025 and Tetrahedron, 1993, 49, 8739) have drawbacks that they use a special reagent, diphenyl phosphorazidate [(PhO).sub.2 P(O)N.sub.3 ] in the synthesis route including the synthesis of starting materials, and that the reaction must be carried out at an extremely low temperature.
Synthesizing method D (International Publication No. W094/14436 and J. Org. Chem., 1994, 59, 4040) and synthesizing method E (International Publication No. W094/14436) have the drawback that the reaction must be carried out at an extremely low temperature in the synthesis route including the synthesis of starting materials.
Under the above circumstances, it has been desired to develop a practical method for synthesizing 2,5-diamino-1,6-diphenyl-3-hydroxyhexane derivatives which eliminates the necessity of heavy metal reagents, special reagents, and extremely low temperatures for reaction.
The present inventors carried out extensive studies, and found novel 2-isoxazoline derivatives and acid addition salts thereof, which are very useful intermediates for 2,5-diamino-1,6-diphenyl-3-hydroxyhexane derivatives which in turn serve as intermediates in the synthesis of medicines such as retrovirus protease inhibitors, a method for preparing the derivatives and salts, and a method for preparing 2,5-diamino-1,6-diphenyl-3-hydroxyhexane derivatives using the novel 2-isoxazoline derivatives.